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A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity Upon Viral Infection and Advanced Age

Joma, Basma H ; Siwapornchai, Nalat ; Vanguri, Vijay K ; Shrestha, Anishma ; Roggensack, Sara E ; Davidson, Bruce A ; Tai, Albert K ; Hakansson, Anders P LU orcid ; Meydani, Simin N and Leong, John M , et al. (2021) In Infection and Immunity 89(8).
Abstract

Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human co-infection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2 months) mice, co-infection triggered bacterial dispersal from the... (More)

Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human co-infection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2 months) mice, co-infection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease and mortality in a fraction of mice. In old mice (20-22 months), co-infection resulted in earlier and more severe disease. Aging was not associated with greater bacterial burdens but rather with more rapid pulmonary inflammation and damage. Both aging and IAV infection led to inefficient bacterial killing by neutrophils ex vivo Conversely, aging and pneumococcal colonization also blunted IFN-α production and increased pulmonary IAV burden. Thus, in this multistep model, IAV promotes pneumococcal pathogenicity by modifying bacterial behavior in the nasopharynx, diminishing neutrophil function, and enhancing bacterial growth in the lung, while pneumococci increase IAV burden likely by compromising a key antiviral response. Thus, this model provides a means to elucidate factors, such as age and co-infection, that promote the evolution of S. pneumoniae from asymptomatic colonizer to invasive pathogen, as well as to investigate consequences of this transition on antiviral defense.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
89
issue
8
article number
00471-20
publisher
American Society for Microbiology
external identifiers
  • scopus:85111012839
  • pmid:34031128
ISSN
1098-5522
DOI
10.1128/IAI.00471-20
language
English
LU publication?
yes
id
7fe5c82b-ab04-4043-b1fd-842ada332993
date added to LUP
2021-05-27 09:47:14
date last changed
2024-08-24 18:31:58
@article{7fe5c82b-ab04-4043-b1fd-842ada332993,
  abstract     = {{<p>Streptococcus pneumoniae (pneumococcus) resides asymptomatically in the nasopharynx but can progress from benign colonizer to lethal pulmonary or systemic pathogen. Both viral infection and aging are risk factors for serious pneumococcal infections. Previous work established a murine model that featured the movement of pneumococcus from the nasopharynx to the lung upon nasopharyngeal inoculation with influenza A virus (IAV) but did not fully recapitulate the severe disease associated with human co-infection. We built upon this model by first establishing pneumococcal nasopharyngeal colonization, then inoculating both the nasopharynx and lungs with IAV. In young (2 months) mice, co-infection triggered bacterial dispersal from the nasopharynx into the lungs, pulmonary inflammation, disease and mortality in a fraction of mice. In old mice (20-22 months), co-infection resulted in earlier and more severe disease. Aging was not associated with greater bacterial burdens but rather with more rapid pulmonary inflammation and damage. Both aging and IAV infection led to inefficient bacterial killing by neutrophils ex vivo Conversely, aging and pneumococcal colonization also blunted IFN-α production and increased pulmonary IAV burden. Thus, in this multistep model, IAV promotes pneumococcal pathogenicity by modifying bacterial behavior in the nasopharynx, diminishing neutrophil function, and enhancing bacterial growth in the lung, while pneumococci increase IAV burden likely by compromising a key antiviral response. Thus, this model provides a means to elucidate factors, such as age and co-infection, that promote the evolution of S. pneumoniae from asymptomatic colonizer to invasive pathogen, as well as to investigate consequences of this transition on antiviral defense.</p>}},
  author       = {{Joma, Basma H and Siwapornchai, Nalat and Vanguri, Vijay K and Shrestha, Anishma and Roggensack, Sara E and Davidson, Bruce A and Tai, Albert K and Hakansson, Anders P and Meydani, Simin N and Leong, John M and Bou Ghanem, Elsa N}},
  issn         = {{1098-5522}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{8}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Infection and Immunity}},
  title        = {{A Murine Model for Enhancement of Streptococcus pneumoniae Pathogenicity Upon Viral Infection and Advanced Age}},
  url          = {{http://dx.doi.org/10.1128/IAI.00471-20}},
  doi          = {{10.1128/IAI.00471-20}},
  volume       = {{89}},
  year         = {{2021}},
}